Nutritionally enhanced fraction from rice bran and method of lowering insulin resistance using same

ABSTRACT

Nutritionally enhanced nutraceutical Hydrophilic and Lipophilic Rice Bran Fractions from rice bran are provided, as well as a method of using the same to reduce Insulin Resistance in animals, especially humans with pre-diabetes and Type 2 diabetes or others with symptoms of Metabolic Syndrome. Provided in various example embodiments are mixtures of elevated levels of nutraceutical compounds, including but not limited to gamma-oryzanol, inositol, ferulic acid, tocotrienols and phytosterols and pharmaceutical and nutritional compositions thereof. Steps are provided including evaluating insulin resistance parameters, initiating therapy including providing therapeutic amounts of Hydrophilic and Lipophilic Rice Bran Fractions from rice bran to treat pre-diabetes and Type 2 diabetes or others with symptoms of Metabolic Syndrome, managing compliance with the therapy, and monitoring and reevaluating the therapy.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. patent application Ser. No.12/882,202, filed on Sep. 15, 2010, which is incorporated herein byreference in its entirety.

FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

None.

TECHNICAL FIELD

The present invention relates to nutritionally enhanced nutraceuticalhydrophilic and lipophilic fractions from rice bran and a method ofusing the same to reduce Insulin Resistance in animals, especiallyhumans with pre-diabetes and Type 2 diabetes or others with symptoms ofMetabolic Syndrome. More particularly, the present invention relates tothe mixture of elevated levels of nutraceutical compounds, including butnot limited to gamma-oryzanol, inositol, ferulic acid, tocotrienols andphytosterols and pharmaceutical and nutritional compositions thereof,and a method of using the same to reduce insulin resistance.

BACKGROUND

Insulin resistance is a physiological condition where the naturalhormone insulin becomes less effective at lowering blood sugars.Depending on physical activity and dietary conditions, blood glucoselevels may rise outside the normal range and cause adverse healtheffects. Fat and muscle cells require insulin to absorb glucose. In adietary state of energy overabundance, cells internally create acascading process in which insulin receptors on the cell membrane nolonger properly interact with insulin. When these cells fail to respondadequately to circulating insulin, glucose is not adequately absorbed,consequently blood glucose levels rise. For many, long periods ofinsulin resistance precede clinical Type 2 diabetes. During this latentperiod of insulin resistance blood glucose may be maintained at nearnormal levels by overcompensation of insulin. It is widely accepted thatthe diabetic state greatly increases the risk for cardiovasculardisease. This process is a continuum and the prediabetic subject alsohas increased cardiovascular disease risks and inflammation that isprimarily associated with insulin resistance.

Convincing evidence has established that insulin resistance is apre-diabetic state that can predict incident Type 2 diabetes relativelyfar into the future. Of the diabetic population in the U.S., 90 to 95%suffer from Type 2 diabetes. According to the American Association ofClinical Endocrinologists, up to 80% of Type 2 diabetics are insulinresistant. Numerous studies have documented the development of insulinresistance as a result of increased intake of dietary fats. In bothanimals and humans, there is an inverse relationship between fastingplasma triglyceride concentration and insulin sensitivity. This medicalresearch associating triglycerides and insulin resistance has practicalapplications. A multifaceted diabetic medical nutrition therapy programthat simultaneously addresses lipids, triglycerides, and insulinresistance can greatly increase the efficacy of a diabetic managementprogram. Recent clinical studies have shown excellent sensitivity atmeasuring insulin resistance with a triglyceride/glucose index. Othershave observed the connections between oxidative stress indicators andlower antioxidant levels.

Elevated Body Mass Index (BMI) is well associated with and the primarycontributor to insulin resistance but the initial events triggering thedevelopment of insulin resistance and its causal relations withderegulation of glucose and fatty acids metabolism remain unclear. Thereis clear evidence that insulin resistance is associated with increasedoxidative stress and that oxidative stress is the causal agent forinsulin resistance. Oxidative stress also disrupts internal antioxidantmechanisms.

Numerous studies have linked increased oxidative stress to insulinresistance. In diabetics, oxidative stress increased and antioxidantdefenses are diminished. In both normal individuals and Type 2 diabeticpatients, reduction of oxidative stress improved insulin sensitivity aswell as improved Beta-cell function. Most Type 2 diabetics aresignificantly influenced by insulin resistance. A number of researchershave demonstrated that the activities of pathways for reactive oxygenspecies (ROS) production and oxidative stress increase in liver, muscleand fat tissue in animals and humans before the onset of insulinresistance. Reducing insulin resistance also offers a protective effecton beta-cells. This is very important for the long-term preservation ofinsulin secretion. Clinical trials have demonstrated improvement ofinsulin sensitivity in insulin resistance and diabetic patients treatedwith antioxidants.

Recent landmark research from M.I.T. and the Harvard Medical Schoolindicates that increased oxidative stress levels are an importanttrigger and causal agent for insulin resistance in numerousphysiological settings and that antioxidants were able to decreaseinsulin resistance caused by oxidative stress. Other researchers havealso found that glycemic control and oxidative stress are seen to betightly related, and improving glycemic control is associated with alowering of oxidative stress. Reducing oxidative stress can also improveglycemic control. Antioxidants have been shown to reduce oxidativestress and in turn improve insulin secretion and decrease insulinresistance in diabetics. Accordingly, medical nutrition therapy forhumans concerned with diabetes should include decreasing fatty acids andincreasing intake of effective antioxidants.

Antioxidants should be administered in an effective manner. Manyantioxidants work only in specific chemical reactions within the body.Thus, single antioxidant dosages may overload the body with oneantioxidant, and saturate that one chemical reaction, but not addressthe more complex and holistic oxidative stress problem. Some oxidativestress occurs within the cell with over-production of mitochondrialNADH. Many antioxidants are not able to provide intracellular relief ofoxidative stress. Antioxidants have demonstrated the ability to decreaseoxidative stress, thus preserving Beta-cell function, increasing insulinsensitivity, protecting vascular cell integrity, and repairing nerves indiabetes damaged organs. Additionally, oxidative stress has beendocumented to inversely affect mitochondrial activity and oxidativestress has been found to be a relevant negative regulator of insulinsecretion. Because of the negative effects of oxidative stress,nutrition experts suggest that daily intake should be at least 3,000 to5,000 Oxygen Radical Absorbance Capacity (“ORAC”) units to have asignificant impact on plasma and tissue antioxidant capacity. Accordingto estimates however, the average American consumes only 1,000 to 2,000ORAC units per day. What is needed therefore is a nutritional supplementthat makes up for this deficiency in daily antioxidant intake of ORACunits.

SUMMARY

The present inventors have discovered that the enhanced enzymaticextraction processing of enhanced rice bran hydrophilic and lipophilicfractions yields elevated levels of nutraceutical components that can beadministered in such a way as to reduce insulin resistance. Thesecompounds are more bioavailable to humans due to enhanced enzymaticprocessing.

Rice bran is a nutrient-dense composition derived from the milling ofrice. Rice bran is a rich source of protein, fat, carbohydrate and anumber of micronutrients such as vitamins, minerals, antioxidants,phytochemicals and phytosterols. The nutritional value of rice bran hasbeen well recognized. Use of rice bran in treatment of a number of humanailments, such as diabetes, coronary diseases, arthritis, and cancer,have been described in the following U.S. Patents and published patentapplications including: U.S. Pat. No. 5,985,344, issued Nov. 16, 1999,entitled, “Process for Obtaining Micronutrient Enriched Rice Bran Oil;”U.S. Pat. No. 6,126,943, issued Oct. 3, 2000, and entitled, “Method forTreating Hypercholesterolemia, Hyperlipidemia, and Atherosclerosis;”U.S. Pat. No. 6,303,586 issued Oct. 16, 2001, and entitled “SupportiveTherapy for Diabetes, Hyperglycemia and Hypoglycemia;” U.S. Pat. No.6,350,473, issued Feb. 26, 2002 and entitled “Method for TreatingHypercholesterolemia, Hyperlipidemia, and Atherosclerosis;” U.S. Pat.No. 6,558,714, issued May 6, 2003, and entitled “Method for TreatingHypercholesterolemia, Hyperlipidemia, and Atherosclerosis;” U.S. Pat.No. 6,733,799 issued May 11, 2004, and entitled “Method for TreatingHypercholesterolemia, Hyperlipidemia, and Atherosclerosis;” and U.S.Pat. No. 6,902,739, issued Jun. 7, 2005, and entitled “Method forTreating Joint Inflammation, Pain, and Loss of Mobility,” and U.S.Patent Application Publication US 2008/0038385 entitled “Therapeuticuses of an anti-cancer composition derived from rice bran.” Additionalutilizations of rice bran have been described in U.S. Patent ApplicationPublication US 2009/0285919 entitled “Rice Bran Extracts forInflammation and Methods of Use Thereof;” U.S. Patent ApplicationPublication US 2009/0220666 entitled “Utilization of Stabilized Bran inHigh Protein Products;” U.S. Patent Application Publication US2009/0191308 entitled “Method of Preparing Emulsified Cereal BranDerivatives;” and U.S. Patent Application Publication US 2009/0162514entitled “Production of Pasta Using Rice Bran and Rice Flour.” Each andevery one of the foregoing patents and published patent applications arehereby incorporated herein by reference in their entireties for all thatthey teach and describe.

The present invention relates to the use of end-products of the processof producing nutritionally enhanced nutraceutical hydrophilic andlipophilic fractions from rice bran, which process is described in U.S.patent application Ser. No. 12/882,202, filed on Sep. 15, 2010, which isincorporated herein by reference in its entirety. Such end-products areavailable from Diabco Life Sciences LLC under the brand name Nutra-Iso™.It has been discovered that these end-products may be used in a methodas described herein to reduce Insulin Resistance in animals, especiallyhumans with pre-diabetes and Type 2 diabetes or others with symptoms ofMetabolic Syndrome.

More generally, the inventors have discovered that the mixture ofelevated levels of nutraceutical compounds including but not limited toany of gamma-oryzanol, inositol, ferulic acid, tocotrienols andphytosterols and pharmaceutical and nutritional compositions thereof,may be used in a method as described herein to supplement medicalnutrition therapy and reduce insulin resistance. These nutraceuticallevels may be obtained by a series of enzymatic extractions that havebeen found to yield significantly more bioavailable levels of thesecompounds. For example, the inventors have discovered that theNutra-Iso™ brand nutraceutical hydrophilic and lipophilic fractions havesignificantly increased bioavailability and increased nutraceuticalcontent that may be used to successfully reduce insulin resistance.

Accordingly, what is described herein is a nutraceutical antioxidantcomplex specially adapted for the treatment, management, and/orprevention of insulin resistance and other conditions in animals,especially humans. Provided is a composition and method for treating,managing or preventing insulin resistance in animals, especially humans,that employs a safe and effective nutraceutical antioxidant complex,without pro-oxidation activity, while providing a beneficial effect tothe blood profile. Also provided is an orally delivered compositionuseful for treating, managing or preventing insulin resistance inanimals, especially humans. Further provided is a nutraceuticalantioxidant complex for treating animals, especially humans with insulinresistance.

Also provided are compositions of a nutraceutical antioxidant complexwith nutritional fortification to enhance antioxidant synergisms. Thesecompositions may be comprised of dosage units effective to reduceinsulin resistance levels, such as about 5-50 mg gamma-oryzanol, 10-200mg of inositol, 5-50 mg ferulic acid, 2-25 mg tocotrienols, and 20-50 mgphytosterols of these nutraceutical antioxidants per day and a completecomplex dosage of 5 to 60 gram per day administered once or twice a day.

In various example embodiments, provided is a unique formulation ofantioxidants in combination with hydrophilic and lipophilic fractionsthat provides approximately two to four times the minimum recommendeddaily antioxidant intake of ORAC units per day.

In various example embodiments the composition may include anutraceutical antioxidant complex of plant origin having nopro-oxidation activity, wherein antioxidants include soluble andinsoluble polyphenols and phytosterols which can be obtained from thegenus Oryza sativa or Oryza glaberrima.

In various example embodiments the composition may comprise any ofgamma-oryzanols, inositol, ferulic acid, tocotrienols or theirconjugates, including dimers and oligomers, which are suitable for thetreatment, management, or prevention of insulin resistance in animals,especially humans.

The nutraceutical antioxidant complex may be prepared through multipleenzymatic processes that may comprise of the steps of: adding at leastthree enzymes to the slurry separately and heating the slurrysufficiently to activate the given enzymes. These separate enzymaticprocesses enhance the nutritional content of rice bran by furtherextracting soluble and insoluble vitamins, minerals, phytosterols andpolyphenols bound to the fiber component in the rice bran.

The present improvements are achieved by utilizing additional enzymesunder a range of conditions to convert protein and fiber in the ricebran to less complex fractions that can be isolated from insolublefractions by screening and centrifuging. This process is described inU.S. patent application Ser. No. 12/882,202, filed on Sep. 15, 2010,which is incorporated herein by reference in its entirety, and thatprocess is referred to herein as the “Enhanced Enzyme Treatment” andincludes treating rice bran slurries with certain enzymes in single ormultiple process steps to facilitate isolation and inclusion of proteinand fiber into the hydrophilic and lipophilic fraction from rice bran.With the inclusion of the protein, fat, and fiber fractions, the yieldof the finished product is significantly increased in quantity andimproved in nutritional quality. The finished products resulting fromthe Enhanced Enzyme Treatment process are referred to herein as “theHydrophilic and Lipophilic Rice Bran Fractions.” Examples of theHydrophilic and Lipophilic Rice Bran Fractions include Nutra-Iso™ brandproducts available from Diabco Life Sciences LLC. Other aspects of theinvention are disclosed herein as discussed in this specification.

BRIEF DESCRIPTION OF THE DRAWINGS

Various aspects of the invention can be better understood with referenceto the following figures. In the figures, like reference numeralsdesignate corresponding parts throughout the different views. It will beunderstood that certain components and details may not appear in thefigures to assist in more clearly describing the invention.

FIG. 1 is a chart showing typical analytical data of a complex of TheHydrophilic and Lipophilic Rice Bran Fraction resulting from TheEnhanced Enzyme Treatment, according to various example embodiments ofthe invention.

FIG. 2 is flow chart showing example steps of therapeutic processesaccording to various example embodiments of the invention.

DETAILED DESCRIPTION

1. Rice Bran Hydrophilic Fraction

A. Source of Rice Bran Hydrophilic Fraction

The Enhanced Enzyme Treatment process, as defined above, may becompleted with at least three potential end-products or fractions. Theenzymatic slurry may be designed to extract additional nutrientsnormally bound too tightly to the bran fiber to become nutritionallyavailable to animals. The rice bran slurry can be separated intohydrophilic and lipophilic fractions. The soluble fraction may be pumpedfrom the slurry and air dried to specific moisture specifications. Theresulting Hydrophilic and Lipophilic Rice Bran Fraction is high inniacin and B₆ vitamins and also provides significant nutraceuticallevels of gamma-oryzanol, ferulic acid and at least four phytosterols.When tested using the ORAC antioxidant analysis method, the Hydrophilicand Lipophilic Rice Bran Fraction has the highest overall ORAC_(Total)level when compared to other rice bran fractions.

2. Rice Bran Fraction of Hydrophilic and Lipophilic Components

A. Source of Rice Bran Fraction of Hydrophilic and Lipophiliccomponents.

When rice bran is subjected to the Enhanced Enzyme Treatment process, asdefined above, the end-products can be formulated to create solutionswith targeted levels of hydrophilic and lipophilic components. Thisformulated slurry is not only designed to extract additional nutrientsnormally bound too tightly to the bran fiber to become nutritionallyavailable to animals, but further to isolate desired hydrophilic andlipophilic components that have been tested for nutraceutical value.This isolated slurry is then air dried to specific moisturespecifications. This Hydrophilic and Lipophilic Rice Bran Fraction ismore nutritionally robust than the soluble fraction. It is high inniacin, B6, biotin, Choline, copper, magnesium, phosphorus and zinc.This Hydrophilic and Lipophilic Rice Bran Fraction also providessignificant nutraceutical levels of inositol and gamma-oryzanol withlesser levels of ferulic acid and phytosterols. When tested using theORAC antioxidant analysis method, the Hydrophilic and Lipophilic RiceBran Fraction had significant antioxidant levels.

The analytical method used to analyze the antioxidant composition of theHydrophilic and Lipophilic Rice Bran Fractions was developed by USDApersonnel and further validated, using the methods set forth in Opara EC., Oxidative Stress, Micronutrients, Diabetes Mellitus and itsComplications, The Journal of the Royal Society for the Promotion ofHealth, 122:28-34; and Krauss S, et al., Superoxide-mediated activationof uncoupling protein 2 causes pancreatic β cell dysfunction, Journal ofClinical Investigation, 2003, 112:1831-1843. The analysis of antioxidantcapacity of the Hydrophilic and Lipophilic Rice Bran Fractions shown inFIG. 1 was conducted by Brunswick Laboratories, Norton, Mass., utilizingthe published methodology noted above. The test was conducted by Y. Kouand supervised and approved by Boxin Ou, PhD.

B. Nutraceutical Significance of Hydrophilic and Lipophilic Componentsof Interest

Scientific research, in both animal and human subjects, generallyconcludes that there are multiple enzymatic and metabolic actions thatplay interactive roles in reducing insulin resistance, thereby helpingimprove blood glucose metabolism, reducing blood glucose and seruminsulin levels and reducing the health risks associated with diabetes.Preliminary research concludes that this is also the case with theHydrophilic and Lipophilic Rice Bran Fractions. The present Hydrophilicand Lipophilic Rice Bran Fractions are thought to interact in severalways to reduce insulin resistance, as described below.

First, the Hydrophilic and Lipophilic Rice Bran Fractions contain veryhigh levels of a number of polyphenols. These polyphenols havesignificantly higher antioxidant capacity than traditional supplementalvitamins (Vitamin E, C, etc.) In particular, the complex of theinvention is high in natural tocotrienols, ferulic acid,gamma-oryzanols, inositol and several phytosterols. These antioxidants,in combination with over 80 additional natural antioxidants provide anutraceutical foundation for decreasing insulin resistance.

Second, independent laboratory analyses have documented the high naturalantioxidant levels found in the Hydrophilic and Lipophilic Rice BranFractions, as noted in Brunswick Lab ORAC Test Values, 2012, shown inFIG. 1. Vitamin E is known to have eight homologues that are active inglucose metabolism, four each of tocopherols and tocotrienols. Theprimary bioactive function of the tocotrienol complex is its capacity asan antioxidant in improved cellular function and protection of the lipidcell membrane, thereby promoting healthy cellular function and morebalanced blood glucose metabolism. Results indicate that α-tocotrienol,which is contained in the Hydrophilic and Lipophilic Rice BranFractions, may be at least 3-fold more efficient as a scavenger ofperoxyl radicals than conventional vitamin E (α-tocopherol). TheHydrophilic and Lipophilic Rice Bran Fractions contain significantlevels of tocotrienols. In addition, these tocotrienols have beenscientifically documented to lower total cholesterol and LDL cholesterolin blood plasma. Studies suggest that this may be accomplished byinhibiting the activity of the enzyme HMG-CoA which is responsible forcholesterol synthesis in the liver. Micromolar amounts of tocotrienol,but not tocopherol, have been shown to suppress the activity of HMG-CoA.These findings provide insight into how lipid metabolism modificationassociated with the Hydrophilic and Lipophilic Rice Bran Fractionsaffect blood glucose metabolism.

Third, the Hydrophilic and Lipophilic Rice Bran Fractions contain veryhigh levels of natural gamma-oryzanols. Scientific studies haveconfirmed that oryzanol is a natural antioxidant superior totocopherols. The biologically active portion of gamma-oryzanol isferulic acid. Just recently in animal studies, ferulic acidsignificantly decreased the levels of glycogen in the liver and skeletalmuscle along with diminishing the activities of hepaticglucose-6-phosphate dehydrogenase, catalase and peroxidase in whencompared with controls. In addition, gamma-oryzanol has been shown toaffect bile acid secretion and fecal excretion of cholesterol.

3. Nutritional and Nutraceutical Complex of the Hydrophilic andLipophilic Rice Bran Fractions

A. Preparation of the Complex

The complex of the Hydrophilic and Lipophilic Rice Bran Fractions can beprepared by dry blending a fine powder of the Fractions in specificratios in a suitable blender as described below and as described in U.S.patent application Ser. No. 12/882,202, filed on Sep. 15, 2010, which isincorporated herein by reference in its entirety.

4. Pharmaceutical and Nutraceutical Formulation of the Complex of theHydrophilic and Lipophilic Rice Bran Fractions

A. Preparation of Formulations

Pharmaceutical and nutritional formulations of the Hydrophilic andLipophilic Rice Bran Fractions may include suitable pharmaceuticaland/or nutritional excipient(s) that are suitable for oraladministration. Generally, these oral formulations of the invention fallinto one of five categories:

-   -   1. A solution, suspension or syrup that is ready for oral        administration;    -   2. A dry powder composition that can be combined with water just        prior to use, i.e., a reconstitutable composition;    -   3. A liquid concentrate ready for dilution prior to        administration;    -   4. A tablet ready for oral administration; or    -   5. A capsule ready for oral administration.

The orally administered vehicle in these formulations normally has notherapeutic activity and is nontoxic, but presents the activeconstituent to the body tissues in a form appropriate for absorption.Suitable absorption of the complex normally will occur most rapidly andcompletely when the composition is presented as an aqueous solution. Inpreparing formulations which are suitable for oral administration, onecan use aqueous vehicles, water-miscible vehicles, or non-aqueousvehicles. Water-miscible vehicles are also useful in the formulation ofthe composition of the Hydrophilic and Lipophilic Rice Bran Fractions.Another useful formulation is a reconstitutable composition that may bea sterile solid packaged in a dry form. Additional substances may beincluded in the compositions of the Hydrophilic and Lipophilic Rice BranFractions to improve or safeguard the quality of the composition. Anadded substance may affect solubility, provide for patient comfort,enhance the chemical stability, or protect preparation against thegrowth of microorganisms. The composition may also include anappropriate solubilizer, or substances that act as antioxidants, and apreservative to prevent the growth of microorganisms. These substancesmay be present in an amount appropriate for their function, and shouldnot adversely affect the action of the composition.

Preferred pharmaceutical or nutritional formulations are typically thosesuitable for oral administration to warm-blooded animals. Thecompositions herein may contain the complex ingredient alone, or incombination with a pharmaceutically or nutritionally acceptableexcipient, in dosage unit forms such as dry powder, tablets, coatedtablets, hard or soft gelatin capsules or syrups. These administratableforms can be prepared using known procedures, for example, byconventional mixing, granulating, tablet coating, dissolving orlyophilisation processes. Thus, pharmaceutical or nutritionalcompositions for oral administration can be obtained by combining theactive ingredient with solid carriers, optionally granulating theresulting mixture, and processing the mixture by granulation, if desiredor necessary, after the addition of suitable excipients, to give tabletsor coated tablet cores. Dyes or pigments can be added to the tablets orcoated tablets, for example, to identify or indicate different doses ofthe active complex ingredient.

Other pharmaceutical or nutritional preparations suitable for oraladministration are hard gelatin capsules and also soft gelatin capsulesmade, for example, from gelatin and a plasticizer such as glycerol orsorbitol. Hard capsules may include the complex containing theHydrophilic and Lipophilic Rice Bran Fractions in admixture with fillerssuch as lactose, binders such as starches, and/or lubricants such astalc or magnesium stearate, and if desired, stabilizers. In softcapsules, the Hydrophilic and Lipophilic Rice Bran Fractions arepreferably dissolved or suspended in a suitable liquid, such as fattyoil, paraffin oil or a liquid polyethylene glycol, to which a stabilizercan be added.

The Hydrophilic and Lipophilic Rice Bran Fraction complex, when obtainedby dry blending process, converts into true complex when formulated inaqueous or alcoholic systems. Alternately, this dry blended material canget converted into an effective complex when administered to primates,especially human.

B. Other Active Ingredients

The formulations of the invention may include added active ingredientsother than the Hydrophilic and Lipophilic Rice Bran Fraction complexitself, including by way of example and not limitation:

-   -   1. Antioxidants: e.g., Alpha lipoic acid, Coenzyme Q;    -   2. Minerals and Vitamins synergistic to the antioxidant found in        the Hydrophilic and Lipophilic Rice Bran Fractions in their        effect on the oxidative stress complex: e.g., Vitamin C, Vitamin        E, Selenium, Chromium, and Zinc;    -   3. Minerals, Vitamins, or other compounds with laboratory or        clinical evidence of reducing insulin resistance: e.g.,        Chromium, Boron, Carnitine;    -   4. Other Minerals, Vitamins, or other compounds with laboratory        or clinical evidence in decreasing cardiovascular disease risk:        e.g., Vitamin B3, Vitamin B12, Biotin, Folate, B6;    -   5. Other Minerals and Vitamins needed for optimum health: e.g.,        Vitamin B5, Vitamin D, Vitamin K, Calcium, Potassium, and        Magnesium;    -   6. Plant extracts: e.g., American ginseng, Bilberry, Ginkgo        biloba, Garlic and Onions; and    -   7. Any other suitable ingredients.

5. Therapeutic Uses

A user, including an animal or person, can use the Hydrophilic andLipophilic Rice Bran Fractions to reduce insulin resistance as describedherein. FIG. 2 shows example steps of therapeutic processes according tovarious example embodiments of the invention.

Step 1, monitor and evaluate, includes measuring health and insulinresistance parameters. Currently there is no clinically efficient methodof effectively and directly measuring insulin resistance. Instead,clinicians look at measurable symptoms relating to insulin resistance tomanage and reduce the risks associated with insulin resistance. TheAmerican Association of Clinical Endocrinology (AACE) has created aposition statement on insulin resistance syndrome that summarizes theeffective clinical symptoms associated with insulin resistance. Thediagnosis of the insulin resistance syndrome according to AACE is basedon clinical judgment in view of various factors and symptoms. Forexample, following are clinical symptoms endocrinologists use to measureand manage insulin resistance:

-   -   1. Triglycerides above 1.7 mmol/l (150 mg/dl);    -   2. HDL-cholesterol for men less than 1.03 mmol/l (40 mg/dl) and        for women less than 1.29 mmol/l (50 mg/dl);    -   3. Blood pressure above 130/85 mmHg; and    -   4. Plasma glucose, either fasting of 6.1-6.9 mmol/l (110-125        mg/dl) or 2-hour post-glucose challenge of 7.8-11.1 mmol/l        (140-200 mg/dl).

Other factors to be considered in the diagnosis in Step 1 areoverweight/obesity (body mass index over 25 kg/m²), a family history ofType 2 diabetes, polycystic ovary syndrome, sedentary lifestyle,advancing age, and ethnic groups particularly susceptible to Type 2diabetes.

The present therapies may be indicated for humans with pre-diabeticcondition fasting glucose levels of 100 to 120 mg/dL along with elevatedLDL cholesterol or elevated triglycerides and blood pressure at or above130/85 mmHg. For the diabetic human, the most serious symptom ofelevated blood sugar has already been diagnosed. If the human also haselevated blood pressure (exceeding 130/85 mmHg) and elevated LDLcholesterol or elevated triglycerides, then the human should begintherapy as described below with respect to Step 2 shown in FIG. 2.

Step 2 comprises initiating therapy by using or providing the user witha therapeutic amount of the Hydrophilic and Lipophilic Rice BranFractions. In various example embodiments, a dosage range of 5 grams to30 grams of a combination of the Hydrophilic and Lipophilic Rice BranFractions may be administered once, twice or three times daily. Dosagerange and frequency may be determined by estimated duration ofexperiencing insulin resistance, severity of fasting glucose levels,triglyceride levels, overall physical activity and obesity. Forpre-diabetic humans, a typical therapy may begin with a 10 to 20 gramdosage of the Hydrophilic and Lipophilic Rice Bran Fractions, twicedaily for 90 days. For Type 2 diabetic humans, estimated duration of thediabetic condition, blood sugar, lipid and triglyceride levels may beconsidered in developing a therapeutic program. When A1c levels exceed7.2% with elevated lipids and triglycerides, a diabetic human may begintherapy with a 20 to 30 gram dose taken two to three times daily.

As mentioned in the American Association of Clinical Endocrinology(AACE) position statement, ethnicity can also play a role in theaggressiveness of initiating therapy and therapeutic dosage andfrequency. African-Americans, Hispanics, Pacific Islanders, and NativeAmerican Indians are more susceptible than Caucasians to Type 2 diabetesand thus should begin therapy earlier in symptom progression and withmore aggressive overall therapy, i.e., higher dosage and/or greaterfrequency.

Delivery of the Hydrophilic and Lipophilic Rice Bran Fractions could bein the form of a dry powder, tablets, coated tablets, hard or softgelatin capsules, syrups, or any other suitable delivery means.

It may also be helpful to prescribe or obtain nutrition and physicalactivity coaching as part of the therapy or to complement the therapy.

In Step 3 compliance with the therapy is managed. The patient or usermay be contacted periodically or regularly, for instance at least every30 days in certain embodiments. When contacted, the patient or user maybe coached to help them continue with the therapy, including encouragingthe user to consume the Hydrophilic and Lipophilic Rice Bran Fractionsat prescribed intervals and to comply with any nutrition and physicalactivity programs.

Turning to Step 4, the therapy may be periodically monitored andreevaluated. For instance, at the end of the 90-day or other designatedperiod blood may be drawn for glucose and lipid profile analysis. Bloodpressure may also be recorded. If blood glucose and lipid profiles haveimproved measurably, for instance after A1c levels decreased to 5.7%,then a revised therapy may be initiated. A revised therapy may comprisea preventative or maintenance therapy, such as a single 10 to 20 gramdosage of the Hydrophilic and Lipophilic Rice Bran Fractions taken dailywith a meal (preferably breakfast). Such a preventative or maintenancetherapy may continue until BMI decreases below 24 and blood sugar andlipid profiles remain within healthy ranges for a long period of time,especially when the human has been in the diabetic state for anextensive period of time. If there is a change in the monitoredparameters requiring a different or new therapy, then the processreturns to Step 1 and repeats.

In various embodiments, any or all of Steps 1, 2, 3 or 4 might beomitted. For example, while it is not advised, in practice a user mightsimply obtain some of the Hydrophilic and Lipophilic Rice Bran Fractionsand self-administer a therapeutic amount, for instance based oninstructions on a product container or in advertising material or evenin this patent, and thereby obtain some or all of the benefits describedherein.

Based on clinical results applying the methods described herein, thelikelihood of measurable decreases in insulin resistance parameters isin the range of 80 to 90 percent.

As will be apparent to persons skilled in the art, modifications andadaptations to the above-described example embodiments of the inventioncan be made without departing from the spirit and scope of theinvention, which is defined only by the following claims.

The invention claimed is:
 1. A nutraceutical, comprising: a therapeuticamount of a hydrophilic and lipophilic rice bran fraction prepared by anenzyme treatment, wherein said amount is sufficient to treat InsulinResistance in a user, and wherein said fraction has a total OxygenRadical Absorbance Capacity of at least 20,500 micromoles Troloxequivalents per 100 grams of said fraction, and wherein said enzymetreatment comprises the use of a beta-glucanase enzyme, a thermotolerantprotease enzyme mix derived from Carica papaya, and a thermostablealpha-amylase enzyme.
 2. The nutraceutical of claim 1, furthercomprising: therapeutic amounts of hydrophilic and lipophilic fractionsfrom rice bran sufficient to treat pre-diabetes in a user.
 3. Thenutraceutical of claim 1, further comprising: therapeutic amounts ofhydrophilic and lipophilic fractions from rice bran sufficient to treatType 2 diabetes in a user.
 4. The nutraceutical of claim 1, furthercomprising: therapeutic amounts of hydrophilic and lipophilic fractionsfrom rice bran sufficient to treat Metabolic Syndrome in a user.
 5. Thenutraceutical of claim 1, wherein: the therapeutic amounts ofhydrophilic and lipophilic fractions from rice bran comprise 5 grams to30 grams of the hydrophilic and lipophilic fractions from rice bran. 6.The nutraceutical of claim 1, wherein: the therapeutic amounts ofhydrophilic and lipophilic fractions from rice bran comprise 10 grams to20 grams of the hydrophilic and lipophilic fractions from rice bran. 7.The nutraceutical of claim 1, wherein the hydrophilic and lipophilicfractions from rice bran are in a solution, suspension, or syrup, andare ready for oral administration.
 8. The nutraceutical of claim 1,wherein the hydrophilic and lipophilic fractions from rice bran are in adry powder composition adapted to be combined with water prior toadministration.
 9. The nutraceutical of claim 1, wherein the hydrophilicand lipophilic fractions from rice bran are in a liquid concentrateadapted to be diluted prior to administration.
 10. The nutraceutical ofclaim 1, wherein the hydrophilic and lipophilic fractions from rice branare in a tablet ready for oral administration.
 11. The nutraceutical ofclaim 1, wherein the hydrophilic and lipophilic fractions from rice branare in a capsule ready for oral administration.
 12. The nutraceutical ofclaim 1, further comprising two or more of any of the following: Alphalipoic acid; Coenzyme Q; Vitamin C; Vitamin E; Selenium; Chromium; Zinc;Chromium; Boron; Carnitine; Vitamin B3; Vitamin B12; Biotin; Folate;Vitamin B6; Vitamin B5; Vitamin 0; Vitamin K; Calcium; Potassium;Magnesium; Ginseng; Bilberry; Ginkgo biloba; Garlic; Onions.
 13. Amethod of treating Insulin Resistance in a user, comprising the stepsof: providing the user with a nutraceutical comprising a therapeuticamount of a hydrophilic and lipophilic rice bran fraction prepared by anenzyme treatment, wherein said amount is sufficient to treat InsulinResistance in the user, and wherein said fraction has a total OxygenRadical Absorbance Capacity of at least 20,500 micromoles Troloxequivalents per 100 grams of said fraction, and wherein said enzymetreatment comprises the use of a beta-glucanase enzyme, a thermotolerantprotease enzyme mix derived from Carica papaya, and a thermostablealpha-amylase enzyme.
 14. The method of claim 13, further comprising thestep of: providing the user with a nutraceutical comprising therapeuticamounts of hydrophilic and lipophilic fractions from rice bransufficient to treat pre-diabetes in a user.
 15. The method of claim 13,further comprising the step of: providing the user with a nutraceuticalcomprising therapeutic amounts of hydrophilic and lipophilic fractionsfrom rice bran sufficient to treat Type 2 diabetes in a user.
 16. Themethod of claim 13, further comprising the step of: providing the userwith a nutraceutical comprising therapeutic amounts of hydrophilic andlipophilic fractions from rice bran sufficient to treat MetabolicSyndrome in a user.
 17. The method of claim 13, wherein: the therapeuticamounts of hydrophilic and lipophilic fractions from rice bran comprise5 grams to 30 grams of the hydrophilic and lipophilic fractions fromrice bran.
 18. The method of claim 13, wherein: the therapeutic amountsof hydrophilic and lipophilic fractions from rice bran comprise 10 gramsto 20 grams of the hydrophilic and lipophilic fractions from rice bran.19. The method of claim 13, wherein: the nutraceutical further comprisestwo or more of any of the following: Alpha lipoic acid; Coenzyme Q;Vitamin C; Vitamin E; Selenium; Chromium; Zinc; Chromium; Boron;Carnitine; Vitamin B3; Vitamin B12; Biotin; Folate; Vitamin B6; VitaminB5; Vitamin D; Vitamin K; Calcium; Potassium; Magnesium; Ginseng;Bilberry; Ginkgo biloba; Garlic; Onions.
 20. A method of treatingInsulin Resistance in a user, comprising the steps of: the userconsuming a nutraceutical comprising a therapeutic amount of ahydrophilic and lipophilic rice bran fraction prepared by an enzymetreatment, wherein said amount is sufficient to treat Insulin Resistancein the user, and wherein said fraction has a total Oxygen RadicalAbsorbance Capacity of at least 20,500 micromoles Trolox equivalents per100 grams of said fraction, and wherein said enzyme treatment comprisesthe use of a beta-glucanase enzyme, a thermotolerant protease enzyme mixderived from Carica papaya, and a thermostable alpha-amylase enzyme.